Creatine and L-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish.

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

Short term creatine loading improves strength endurance even without changing maximal strength, RPE, fatigue index, blood lactate, and mode state.

Creatine is consumed by athletes to increase strength and gain muscle. The aim of this study was to evaluate the effects of creatine supplementation on maximal strength and strength endurance. Twelve strength-trained men (25.2 ± 3.4 years) supplemented with 20 g Creatina + 10g maltodextrin or placebo (20g starch + 10g maltodextrin) for five days in randomized order. Maximal strength and strength endurance (4 sets 70% 1RM until concentric failure) were determined in the bench press. In addition, blood lactate, rate of perceived effort, fatigue index, and mood state were evaluated. All measurements were performed before and after the supplementation period. There were no significant changing in maximal strength, blood lactate, RPE, fatigue index, and mood state in either treatment. However, the creatine group performed more repetitions after the supplementation (Cr: Δ = +3.4 reps, p = 0.036, g = 0.53; PLA: Δ = +0.3reps, p = 0.414, g = 0.06), and higher total work (Cr: Δ = +199.5au, p = 0.038, g = 0.52; PLA: Δ = +26.7au, p = 0.402, g = 0.07). Creatine loading for five days allowed the subjects to perform more repetitions, resulting in greater total work, but failed to change the maximum strength.

Diabetes-related clinical and microstructural white matter changes in patients with Alzheimer's disease.

AIM: Although there exists substantial epidemiological evidence indicating an elevated risk of dementia in individuals with diabetes, our understanding of the neuropathological underpinnings of the association between Type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) remains unclear. This study aims to unveil the microstructural brain changes associated with T2DM in AD and identify the clinical variables contributing to these changes. METHODS: In this retrospective study involving 64 patients with AD, 31 individuals had concurrent T2DM. The study involved a comparative analysis of diffusion tensor imaging (DTI) images and clinical features between patients with and without T2DM. The FSL FMRIB software library was used for comprehensive preprocessing and tractography analysis of DTI data. After eddy current correction, the "bedpost" model was utilized to model diffusion parameters. Linear regression analysis with a stepwise method was used to predict the clinical variables that could lead to microstructural white matter changes. RESULTS: We observed a significant impairment in the left superior longitudinal fasciculus (SLF) among patients with AD who also had T2DM. This impairment in patients with AD and T2DM was associated with an elevation in creatine levels. CONCLUSION: The white matter microstructure in the left SLF appears to be sensitive to the impairment of kidney function associated with T2DM in patients with AD. The emergence of AD in association with T2DM may be driven by mechanisms distinct from the typical AD pathology. Compromised renal function in AD could potentially contribute to impaired white matter integrity.

Effects of a Low Dose of Orally Administered Creatine Monohydrate on Post-Fatigue Muscle Power in Young Soccer Players.

The use of creatine monohydrate (Cr) in professional soccer is widely documented. However, the effect of low doses of Cr on the physical performance of young soccer players is unknown. This study determined the effect of a low dose of orally administered Cr on muscle power after acute intra-session fatigue in young soccer players. Twenty-eight young soccer players (mean age = 17.1 ± 0.9 years) were randomly assigned to either a Cr (n = 14, 0.3 g·kg-1·day-1 for 14 days) or placebo group (n = 14), using a two-group matched, double-blind, placebo-controlled design. Before and after supplementation, participants performed 21 repetitions of 30 m (fatigue induction), and then, to measure muscle power, they performed four repetitions in half back squat (HBS) at 65% of 1RM. Statistical analysis included a two-factor ANOVA (p ˂ 0.05). Bar velocity at HBS, time: p = 0.0006, ŋp2 = 0.22; group: p = 0.0431, ŋp2 = 0.12, time × group p = 0.0744, ŋp2 = 0.02. Power at HBS, time: p = 0.0006, ŋp2 = 0.12; group: p = 0.16, ŋp2 = 0.06, time × group: p = 0.17, ŋp2 = 0.009. At the end of the study, it was found that, after the induction of acute intra-session fatigue, a low dose of Cr administered orally increases muscle power in young soccer players.

Replacing sedentary time for physical activity: Does intensity matter for body composition in oldest-old adults?

To assess the independent and combined relationships among objectively measured sedentary time (ST), light intensity PA (LPA), and moderate-to-vigorous intensity PA (MVPA) with muscle mass and fat mass (FM) and how theoretical displacement of these inter-dependent behaviours relates to body composition in oldest-old men. A total of 1046 men participating in the year 14 visit of the prospective Osteoporotic Fractures in Men (MrOS) cohort study with complete data for accelerometry, dual x-ray absorptiometry, and deuterated creatine dilution (D3Cr) muscle mass were included in the analysis (84.0 ± 3.8 yrs.). Single, partition, and isotemporal substitution models were used to assess the interrelationships between PA intensities and ST with body composition measures, while controlling for relevant confounders. Replacing 30-min of ST with 30-min of MVPA was associated with lower FM (ß =-0.17, p < 0.001) and higher D3Cr muscle mass, although this was of borderline significance (ß = 0.07, p = 0.05). Replacing 30-min of ST for LPA was associated with lower FM (ß =-0.15, p < 0.001), but there was no effect on D3Cr muscle mass (p > 0.05). Exchanging ST with any intensity of PA is associated with benefits for FM in oldest-old adult men, although substitution with MVPA may be more beneficial than LPA for maintaining/improving skeletal muscle mass.

Dodecyl creatine ester therapy: from promise to reality.

Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay. There are no treatments to improve neurodevelopmental outcomes for creatine transporter deficiency (CTD). In this spotlight, we summarize recent advances in innovative molecules to treat CTD, with a focus on dodecyl creatine ester, the most promising drug candidate.

A protocol for remote collection of skeletal muscle mass via D3-creatine dilution in community-dwelling postmenopausal women from the Women's Health Initiative.

BACKGROUND: There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors. METHODS: This study protocol describes the use of a novel method of muscle mass measurement, D3-creatine dilution method (D3Cr), in a large sample (n~6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass. DISCUSSION: The D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups.

Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression (CREATINE-52): a protocol for a double-blind randomized controlled trial.

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

Impact of Short-Term Creatine Supplementation on Muscular Performance among Breast Cancer Survivors.

Breast cancer (BC) is one of the most common cancers in the United States. Advances in detection and treatment have resulted in an increased survival rate, meaning an increasing population experiencing declines in muscle mass and strength. Creatine supplementation has consistently demonstrated improvements in strength and muscle performance in older adults, though these findings have not been extended to cancer populations. PURPOSE: The purpose of this study was to investigate the effects of short-term creatine supplementation on muscular performance in BC survivors. METHODS: Using a double-blind, placebo-controlled, randomized design, 19 female BC survivors (mean ± SD age = 57.63 ± 10.77 years) were assigned to creatine (SUPP) (n = 9) or dextrose placebo (PLA) (n = 10) groups. The participants completed two familiarization sessions, then two test sessions, each separated by 7 days, where the participants supplemented with 5 g of SUPP or PLA 4 times/day between sessions. The testing sessions included sit-to-stand power, isometric/isokinetic peak torque, and upper/lower body strength via 10 repetition maximum (10RM) tests. The interaction between supplement (SUPP vs. PLA) and time (Pre vs. Post) was examined using a group × time ANOVA and effect sizes. RESULTS: No significant effects were observed for sit-to-stand power (p = 0.471; ηp2 = 0.031), peak torque at 60°/second (p = 0.533; ηp2 = 0.023), peak torque at 120°/second (p = 0.944; ηp2 < 0.001), isometric peak torque (p = 0.905; ηp2 < 0.001), 10RM chest press (p = 0.407; ηp2 = 0.041), and 10RM leg extension (p = 0.932; ηp2 < 0.001). However, a large effect size for time occurred for the 10RM chest press (ηp2 = 0.531) and leg extension (ηp2 = 0.422). CONCLUSION: Seven days of creatine supplementation does not influence muscular performance among BC survivors.

Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review.

Creatine supplementation has been put forward as a possible aid to cognition, particularly for vegans, vegetarians, the elderly, sleep deprived and hypoxic individuals. However, previous narrative reviews have only provided limited support for these claims. This is despite the fact that research has shown that creatine supplementation can induce increased brain concentrations of creatine, albeit to a limited extent. We carried out a systematic review to examine the current state of affairs. The review supported claims that creatine supplementation can increases brain creatine content but also demonstrated somewhat equivocal results for effects on cognition. It does, however, provide evidence to suggest that more research is required with stressed populations, as supplementation does appear to significantly affect brain content. Issues with research design, especially supplementation regimens, need to be addressed. Future research must include measurements of creatine brain content.

Eight-Week Creatine-Glucose Supplementation Alleviates Clinical Features of Long COVID.

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η2=0.72; left paracentral grey matter F=19.243, p=0.019; partial η2=0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

BACKGROUND: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects. METHODS: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 50.2 ± 3.4 mL kg-1 min-1) to 5 days of creatine monohydrate (0.3 g kg-1 per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg-1) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg-1), sodium bicarbonate (0.3 g kg-1), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial. RESULTS: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects. CONCLUSION: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance.

Comparing the efficacy of concomitant treatment of resistance exercise and creatine monohydrate versus multiple individual therapies in age related sarcopenia.

Aging-related sarcopenia is a degenerative loss of strength and skeletal muscle mass that impairs quality of life. Evaluating NUDT3 gene and myogenin expression as new diagnostic tools in sarcopenia. Also, comparing the concomitant treatment of resistance exercise (EX) and creatine monohydrate (CrM) versus single therapy by EX, coenzyme Q10 (CoQ10), and CrM using aged rats. Sixty male rats were equally divided into groups. The control group, aging group, EX-treated group, the CoQ10 group were administered (500 mg/kg) of CoQ10, the CrM group supplied (0.3 mg/kg of CrM), and a group of CrM concomitant with resistance exercise. Serum lipid profiles, certain antioxidant markers, electromyography (EMG), nudix hydrolase 3 (NUDT3) expression, creatine kinase (CK), and sarcopenic index markers were measured after 12 weeks. The gastrocnemius muscle was stained with hematoxylin-eosin (H&E) and myogenin. The EX-CrM combination showed significant improvement in serum lipid profile, antioxidant markers, EMG, NUDT3 gene, myogenin expression, CK, and sarcopenic index markers from other groups. The NUDT3 gene and myogenin expression have proven efficient as diagnostic tools for sarcopenia. Concomitant treatment of CrM and EX is preferable to individual therapy because it reduces inflammation, improves the lipid serum profile, promotes muscle regeneration, and thus has the potential to improve sarcopenia.

High-dose short-term creatine supplementation without beneficial effects in professional cyclists: a randomized controlled trial.

BACKGROUND: Growing evidence supports the ergogenic effects of creatine supplementation on muscle power/strength, but its effects on endurance performance remain unclear. We assessed the effects of high-dose short-term creatine supplementation in professional cyclists during a training camp. METHODS: The study followed a double-blind, randomized parallel design. Twenty-three professional U23 cyclists (19 ± 1 years, maximum oxygen uptake: 73.0 ± 4.6 mL/kg/min) participated in a 6-day training camp. Participants were randomized to consume daily either a recovery drink (containing carbohydrates and protein) with a 20-g creatine supplement (creatine group, n = 11) or just the recovery drink (placebo group, n = 12). Training loads and dietary intake were monitored, and indicators of fatigue/recovery (Hooper index, countermovement jump height), body composition, and performance (10-second sprint, 3-, 6-, and 12-minute time trials, respectively, as well as critical power and W') were assessed as study outcomes. RESULTS: The training camp resulted in a significant (p < 0.001) increase of training loads (+50% for total training time and + 61% for training stress score, compared with the preceding month) that in turn induced an increase in fatigue indicators (significant time effect [p < 0.001] for delayed-onset muscle soreness, fatigue, and total Hooper index) and a decrease in performance (significant time effect [p = 0.020] for critical power, which decreased by -3.8%). However, no significant group-by-time interaction effect was found for any of the study outcomes (all p > 0.05). CONCLUSIONS: High-dose short-term creatine supplementation seems to exert no consistent beneficial effects on recovery, body composition or performance indicators during a strenuous training period in professional cyclists.

Review of the evidence of radioprotective potential of creatine and arginine as dietary supplements.

PURPOSE: Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes' workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups. CONCLUSIONS: Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD70/30 dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr-Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now.

Creatine and pregnancy outcomes: a prospective cohort study of creatine metabolism in low-risk pregnant females.

BACKGROUND: Physiological adaptations during pregnancy alter nutrient and energy metabolism. Creatine may be important for maintaining cellular energy homeostasis throughout pregnancy. However, the impact of pregnancy on endogenous and exogenous creatine availability has never been comprehensively explored. OBJECTIVES: To undertake a prospective cohort study and determine the physiological ranges of creatine and associated metabolites throughout human pregnancy. METHODS: Females with a singleton low-risk pregnancy were recruited at an Australian health service. Maternal blood and urine were collected at 5-time points from 10-36 weeks of gestation, and cord blood and placental samples were collected at birth. Creatine and associated amino acids and metabolites of creatine synthesis were analyzed. Dietary data were captured to determine effects of exogenous creatine intake. Associations between creatine metabolism and neonatal growth parameters were examined. RESULTS: Two hundred and eighty-two females were included. Maternal plasma creatine remained stable throughout pregnancy [ß: -0.003 µM; 95% confidence interval (CI): -0.07, 0.07; P = 0.94], though urinary creatine declined in late gestation (ß: 0.38 µM/mmol/L creatinine (CRN); 95% CI: -0.47, -0.29; P < 0.0001). Plasma guanidinoacetate (GAA; the precursor to creatine during endogenous synthesis) fell from 10-29 weeks of gestation before rising until birth (ß: -0.38 µM/mmol/L CRN; 95% CI: -0.47, -0.29; P < 0.0001). Urinary GAA followed an opposing pattern (ß: 2.52 µM/mmol/L CRN; 95% CI: 1.47, 3.58, P < 0.001). Animal protein intake was positively correlated with maternal plasma creatine until ∼32 weeks of gestation (ß: 0.07-0.18 µM; 95% CI: 0.006, 0.25; P ≤ 0.001). There were no links between creatine and neonatal growth, but increased urinary GAA in early pregnancy was associated with a slight reduction in head circumference at birth (ß: -0.01 cm; 95% CI: -0.02, -0.004; P = 0.003). CONCLUSIONS: Although maternal plasma creatine concentrations were highly conserved, creatine metabolism appears to adjust throughout pregnancy. An ability to maintain creatine concentrations through diet and shifts in endogenous synthesis may impact fetal growth. This trial was registered at [registry name] as ACTRN12618001558213.

The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.

Despite the known beneficial effects of creatine in treating exercise-induced muscle damage (EIMD), its effectiveness remains unclear. This study investigates the recovery effect of creatine monohydrate (CrM) on EIMD. Twenty healthy men (21-36 years) were subjected to stratified, randomized, double-blind assignments. The creatine (CRE) and placebo (PLA) groups ingested creatine and crystalline cellulose, respectively, for 28 days. They subsequently performed dumbbell exercises while emphasizing eccentric contraction of the elbow flexors. The EIMD was evaluated before and after exercise. The range of motion was significantly higher in the CRE group than in the PLA group 24 h (h) post exercise. A similar difference was detected in maximum voluntary contraction at 0, 48, 96, and 168 h post exercise (p = 0.017-0.047). The upper arm circumference was significantly lower in the CRE group than in the PLA group at 48, 72, 96, and 168 h post exercise (p = 0.002-0.030). Similar variation was observed in the shear modulus of the biceps brachii muscle at 96 and 168 h post exercise (p = 0.003-0.021) and in muscle fatigue at 0 and 168 h post exercise (p = 0.012-0.032). These findings demonstrate CrM-mediated accelerated recovery from EIMD, suggesting that CrM is an effective supplement for EIMD recovery.

Clinical Characteristics, Developmental Trajectory, and Caregiver Burden of Patients With Creatine Transporter Deficiency (SLC6A8).

BACKGROUND AND OBJECTIVES: Creatine transporter deficiency (CTD) is a rare X-linked genetic disorder characterized by intellectual disability (ID). We evaluated the clinical characteristics and trajectory of patients with CTD and the impact of the disease on caregivers to identify relevant endpoints for future therapeutic trials. METHODS: As part of a French National Research Program, patients with CTD were included based on (1) a pathogenic SLC6A8 variant and (2) ID and/or autism spectrum disorder. Families and patients were referred by the physician who ordered the genetic analysis through Reference Centers of ID from rare causes and inherited metabolic diseases. After we informed the patients and their parents/guardians about the study, all of them gave written consent and were included. A control group of age-matched and sex-matched patients with Fragile X syndrome was also included. Physical examination, neuropsychological assessments, and caregiver impact were assessed. All data were analyzed using R software. RESULTS: Thirty-one patients (27 male, 4 female) were included (25/31 aged 18 years or younger). Most of the patients (71%) had symptoms at <24 months of age. The mean age at diagnosis was 6.5 years. Epilepsy occurred in 45% (mean age at onset: 8 years). Early-onset behavioral disorder occurred in 82%. Developmental trajectory was consistently delayed (fine and gross motor skills, language, and communication/sociability). Half of the patients with CTD had axial hypotonia during the first year of life. All patients were able to walk without help, but 7/31 had ataxia and only 14/31 could walk tandem gait. Most of them had abnormal fine motor skills (27/31), and most of them had language impairment (30/31), but 12/23 male patients (52.2%) completed the Peabody Picture Vocabulary Test. Approximately half (14/31) had slender build. Most of them needed nursing care (20/31), generally 1-4 h/d. Adaptive assessment (Vineland) confirmed that male patients with CTD had moderate-to-severe ID. Most caregivers (79%) were at risk of burnout, as shown by Caregiver Burden Inventory (CBI) > 36 (significantly higher than for patients with Fragile X syndrome) with a high burden of time dependence. DISCUSSION: In addition to clinical endpoints, such as the assessment of epilepsy and the developmental trajectory of the patient, the Vineland scale, PPVT5, and CBI are of particular interest as outcome measures for future trials. TRIAL REGISTRATION INFORMATION: ANSM Registration Number 2010-A00327-32.

Caffeine, but Not Creatine, Improves Anaerobic Power Without Altering Anaerobic Capacity in Healthy Men During a Wingate Anaerobic Test.

There is a lack of evidence on the additional benefits of combining caffeine (CAF) and creatine (CRE) supplementation on anaerobic power and capacity. Thus, the aim of the present study was to test the effects of combined and isolated supplementation of CAF and CRE on anaerobic power and capacity. Twenty-four healthy men performed a baseline Wingate anaerobic test and were then allocated into a CRE (n = 12) or placebo (PLA; n = 12) group. The CRE group ingested 20 g/day of CRE for 8 days, while the PLA group ingested 20 g/day of maltodextrin for the same period. On the sixth and eighth days of the loading period, both groups performed a Wingate anaerobic test 1 hr after either CAF (5 mg/kg of body mass; CRE + CAF and PLA + CAF conditions) or PLA (5 mg/kg of body mass of cellulose; CRE + PLA and PLA + PLA conditions) ingestion. After the loading period, changes in body mass were greater (p < .05) in the CRE (+0.87 ± 0.23 kg) than in the PLA group (+0.13 ± 0.27 kg). In both groups, peak power was higher (p = .01) in the CAF (1,033.4 ± 209.3 W) than in the PLA trial (1,003.3 ± 204.4 W), but mean power was not different between PLA and CAF trials (p > .05). In conclusion, CAF, but not CRE ingestion, increases anaerobic power. Conversely, neither CRE nor CAF has an effect on anaerobic capacity.

Effect of Creatine Supplementation on Body Composition and Malnutrition-Inflammation Score in Hemodialysis Patients: An Exploratory 1-Year, Balanced, Double-Blind Design.

Hemodialysis has a detrimental effect on fat-free mass (FFM) and muscle strength over time. Thus, we aimed to evaluate the effect of creatine supplementation on the body composition and Malnutrition-Inflammation Score (MIS) in patients with chronic kidney disease (CKD) undergoing hemodialysis. An exploratory 1-year balanced, placebo-controlled, and double-blind design was conducted with hemodialysis patients (≥18 years). The creatine group (CG) received 5 g of creatine monohydrate and 5 g of maltodextrin per day and the placebo group (PG) received 10 g of maltodextrin per day. MIS and body composition were analyzed at three time points: pre, intermediate (after 6 months), and post (after 12 months). After 6 months, 60% of patients on creatine experienced an increase in FFM compared to a 36.8% increase for those on placebo. Moreover, 65% of patients on creatine increased their skeletal muscle mass index (SMMI) compared to only 15.8% for those on placebo. Creatine increased intracellular water (ICW) in 60% of patients. MIS did not change after the intervention. In the CG, there was an increase in body weight (p = 0.018), FFM (p = 0.010), SMMI (p = 0.022). CG also increased total body water (pre 35.4 L, post 36.1 L; p = 0.008), mainly due to ICW (pre 20.2 L, intermediate 20.7 L, post 21.0 L; p = 0.016). Long-term creatine supplementation in hemodialysis patients did not attenuate the MIS, but enhanced FFM and SMMI, which was likely triggered by an increase in ICW.